The aim of this project is to develop systems for measuring the frequency of point mutations and DNA loss in male germinal tissue. These systems would have the advantage of testing the human population by means of readily available samples, i.e., spermatozoa. At present enzyme histochemical methods are being developed to detect point mutations in male mice and three enzymes and their inhibitors have been characterized. These enzymes are alpha-glycero-phosphate dehydrogenase, lactate dehydrogenase and succinate dehydrogenase. Preliminary work has started with the FACS-l cell sorter to determine its usefulness in measuring the distribution of DNA content in a population of sperm. It is hoped that this instrument may prove useful in showing changes in the distribution pattern in sperm populations derived from mice treated or untreated with known mutagens.